Mucins are heavily glycosylated proteins, which are synthesized and secreted by epithelial cells lining the gastrointestinal, respiratory and genitourinary tracts. To date, thirteen distinct mucin genes have been identified and these can be divided into two distinct classes, gel-forming mucins and membrane-bound mucins. In salivary secretions, mucins facilitate speech and swallowing, protect oral surfaces against microbial, chemical and mechanical injury and contribute to a selectively permeable diffusion barrier between underlying surfaces and the external environment. These functions have largely been attributed to the major gel-forming mucin in saliva, MG1. Nevertheless, we have recently shown that two membrane-bound mucins, MUC1 and MUC4, are expressed in all major salivary glands, including the parotid glands. While virtually nothing is known about the expression and functional properties of membrane-bound mucins in salivary glands and saliva, our hypothesis is that these molecules form an integral part of the oral host-defense system in the protection of oral epithelial surfaces. The overall goal of this project is to understand the mechanisms by which this occurs. The Specific Aims of this project are to: 1) determine the expression pattern of the membrane-bound mucins MUC1 and MUC4 in major and minor salivary glands and in different glandular secretions. 2) characterize the nature of the interactions between membrane-bound and gel-forming mucins and 3) investigate the role of MUC I and MUC4 in protection of oral epithelial surfaces from microbial attack.